Transcriptome analysis of matched primary tumors and lymph-node metastasis in ER+ and TNBC. (A) Schematic regulators of the metastasis phenotype (MRs) in breast carcinoma, representing the strategy used to generate VIPER inferred candidate master regulators of the metastatic state. (B) VIPER inferred master master regulators for metastatic progression in breast carcinoma, ER+ tumors, and TNBC tumors. The genome wide expression signature is represented in the x-axis and by the color scale on top of the figures, where genes were rank sorted from the most downregulated in the metastasis (leftmost in cyan) to the ones upregulated (rightmost in red). Each transcription factor (TF) regulon is indicated by the red and blue vertical bars, which denote the genes whose expression is induced (red) or repressed (blue) by each TF according to the regulatory model. The enrichment of each regulon on the gene expression signature is indicated by the Normalized Enrichment Score (NES), whose color scale is indicated below the figures, and the associated p value. (C) Heatmap depicting the VIPER-inferred protein activity for the top 20 regulatory proteins selected by their consistent dysregulation in metastases when compared to matched primary tumors. (D) Regulatory relationship between TRIM25 and the putative target transcripts: blue: repression, red: induction, grey: undetermined. The color of the targets are proportional to their differential expression in the METs vs. the primary tumors, red: up-regulated, blue: down-regulated in the METs. See also .